The focus of this program in Physiological Genetics is on the inherited anemias of the mouse, for the purpose of increasing our understanding of mammalian erythropoiesis through the investigation of specific genetic defects. The detection, identification, examination, genetic purification, description, and preservation of mouse models of human disease are essential elements, as is the development of therapeutic methods for the treatment of each disease. Twenty different single gene induced disorders at 12 different genetic loci and 2 with polygenic inheritance are currently maintained and under active investigation in this program. Three of the loci produce hypoplastic anemias, 3 give rise to hemolytic anemia, 4 are iron deficiency disorders producing hypochromia, one is an alpha thallasemia, one is an endocrine disorder producing hypoplasia, and the two with polygenic inheritance give rise to autoimmune hemolytic crises. We employ morphological, physiological, biochemical, and genetic methodologies in perusing our studies. Special interest and emphasis is placed at this time on the biochemical and biophysical evaluation of red cell membrane composition and structure in the "hemolytic disease" group of anemias. Investigations into the nature of the spectrin losses characteristic of the different diseases of this type, the ankyrin deficiency identified in one of these, and their relationship to the distortions observed in lipid bilayer asymmetry are being vigorously persued. With the iron deficiency diseases we are especially concerned with an inherited atransferrinemic condition and the hemochromatosis seen in survivors of this model.